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US008580771B2

(12) United States Patent (10) Patent N0.: US 8,580,771 B2 Schramm et a]. (45) Date of Patent: Nov. 12, 2013

(54) DOSAGE FORM FOR HORMONAL EP 0398460 A2 5/1990 CONTRACEPTION EP 0398460 A3 5/1990 EP 0398460 B1 5/1990 (75) Inventors: Georg Schramm, Stolberg (DE); EP 0398460 A2 11/1990 EP 0398460 A3 11/1990 Eric-Paul Paques, Aachen (DE) W0 WO 86/01402 3/1986 W0 WO 99/53910 10/1999 (73) Assignee: Richter Gedeon Nyrt., Budapest (HU) W0 WO 00/38691 7/2000 W0 WO 00/44385 8/2000 ( * ) Notice: Subject to any disclaimer, the term of this WO 02/22110 A2 3/2002 patent is extended or adjusted under 35 W0 W0 02/094276 A1 11/2002 U.S.C. 154(b) by 2098 days. W0 WO 2004/098517 A2 11/2004

(21) App1.No.: 11/244,974 OTHER PUBLICATIONS (22) Filed: Oct. 6, 2005 “Effect of 21-day and 24-day oral contraceptive regimens containing (60 pg) and ethinyl (15 pg) on ovarian activity”, (65) Prior Publication Data Helen Sullivan et al., Fertility and Sterility, vol. 72, No. 1, Jul. 1999, US 2006/0089338 A1 Apr. 27, 2006 1 15-120. “The safety and contraceptive ef?cacy of a 24-day low-dose oral contraceptive regimen containing gestodene 60 pg and Related US. Application Data 15 pg”, Gestodene Study Group 322, The European (63) Continuation-in-part of application No. 11/009,817, Journal of Contraception and Reproductive Health Care, 1999, ?led on Dec. 10, 2004, noW abandoned, and a (Suppl. 2): 9-15. continuation-in-part of application No. 11/009,938, “Folic Acid Awareness and Use Among Women With A History of a ?led on Dec. 10, 2004. Neural Tube Defect Pregnancy”, Can?eld et al., MMWR Recomm Rep. Sep. 13,2002; 51(RR-13):16-9. (30) Foreign Application Priority Data “Effect of 2 1 -day and 24-day Oral Contraceptive Regimens Contain ing Gestodene (60pg) and Ethinyl Estradiol (15 pg) on Ovarian Activ May 28, 2004 (DE) ...... 10 2004 026 670 ity”, Helen Sullivan et al., Fertility and Sterility, vol. 72, No. 1, Jul. May 28, 2004 (DE) ...... 10 2004 026 671 1999, 115-120. “Properties of Reactively Evaporated Gallium Oxide Thin Films”, (51) Int. Cl. Mar. 1979, XP-000905106, pp. 13-17. A61K 31/56 (2006.01) Acne Resolution Rates: Results of a Single-Blind, Randomized, A61K 31/495 (2006.01) Controlled, Parallel Phase III Trial With EE/CMA (Belara®) and (52) US. Cl. EE/LNG (Microgynon®), I. Worret, et al., Pharmacology and Treat USPC ...... 514/171; 514/169; 514/249 ment, Dermatology 2001; 203:38-44. (58) Field of Classi?cation Search “ acetate versus microniZed in the None sequential combined replacement therapy of the meno See application ?le for complete search history. pause”, C. Pelissier, et al., XP-002349010, Maturitas 40 (2001) 85-94. (56) References Cited Non Final Of?ce Action issued on Mar. 12, 2009 by Examiner for corresponding pending U.S. Appl. No. 11/009,361. U.S. PATENT DOCUMENTS (Continued) 6,190,693 B1* 2/2001 Kafrissen et a1...... 424/451 6,265,393 B1 7/2001 Heinrichs ...... 514/178 6,312,722 B1* 11/2001 Schmidt-GollWitZer Primary Examiner * Sreeni Padmanabhan et a1...... 424/464 6,500,814 B1* 12/2002 Hesch ...... 514/170 Assistant Examiner * Jody Karol 6,511,970 B1 1/2003 Rodriguez (74) Attorney, Agent, or Firm * Jason D. Voight 2002/0010167 A1 1/2002 Grubb ...... 514/182 2002/0061875 A1 5/2002 Gast 2004/0063721 A1 4/2004 Deecher (57) ABSTRACT FOREIGN PATENT DOCUMENTS A dosage form for containing a given DE 4104385 C1 2/1991 number of hormone-containing daily units and a given num DE 4224534 A1 7/1992 ber of hormone-free daily units for daily, oral administration, DE 4308406 C1 3/1993 Where the hormone-containing daily units each contain at DE 4321957 C2 9/1995 DE 3486422 T2 6/1997 most the minimum effective daily amount of folic acid for DE 698 04 918 T2 6/1998 Women and the hormone-free daily units contain at least a DE 19705229 C2 4/1999 multiple of this amount up to the maximum permissible DE 19739916 C2 9/2001 amount of folic acid for Women. DE 69804918 T2 11/2002 DE 60101276 T2 4/2004 EP 0253607 1/1988 EP 0253607 A1 1/1988 13 Claims, No Drawings US 8,580,771 B2 Page 2

(56) References Cited Final Of?ce Action issued on Mar. 23, 2009 by Examiner for corre sponding pending U.S. Appl. No. 11/009,938. OTHER PUBLICATIONS Non Final Of?ce Action issued on Sep. 2, 2009 by Examiner for Non Final Of?ce Action issued on Apr. 16, 2009 by Examiner for corresponding pending U.S. Appl. No. 11/009,362. corresponding pending U.S. Appl. No. 11/348,545. G. Schramm, Contraceptive Ef?cacy and Tolerability of Non Final Of?ce Action issued on Jul. 8, 2008 by Examiner for Zmg/Ethinylestradiol 0.03mg (Belara®), corresponding pending U.S. Appl. No. 11/009,938. Clinical Drug Invest 2002122 (4) pp. 221-231. Non Final Of?ce Action issued on Sep. 3, 2009 by Examiner for corresponding pending U.S. Appl. No. 11/009,938. * cited by examiner US 8,580,771 B2 1 2 DOSAGE FORM FOR HORMONAL each case contain folic acid in a daily amount of >200 pg up CONTRACEPTION to the maximum permissible amount for Women of folic acid. Women of child-bearing age have a daily folic acid require CROSS-REFERENCE TO RELATED ment Which may be adequately met by a healthy diet. Long APPLICATIONS term taking of hormonal contraceptives containing gestagens may lead to an additional folic acid requirement, Which may This application is a Continuation in Part Application of likeWise be met by a healthy diet. HoWever, it is advisable to and claims priority from US. patent application Ser. No. provide Women With a daily dose of the minimum effective 11/009,817, ?led on Dec. 10, 2004, pending, and US. patent daily amount of folic acid. application Ser. No. 11/009,938 ?led on Dec. 10, 2004, pend Accordingly, hormone-containing daily units of the do sage ing, and claims foreign priority to DE 10 2004 026 671.9, form according to the invention may each comprise a daily ?led May 28. 2004. amount of folic acid corresponding to this minimum effective daily amount of folic acid. Preferably, the hormone-contain BACKGROUND OF THE INVENTION ing daily units of the dosage form according to the invention contain 0 to 200 pg of folic acid, particularly preferably 5 to 1. Field of the Invention 200 pg of folic acid. The present invention relates to a dosage form for hor The hormone-containing daily units of the dosage form monal contraception containing a given number of hormone according to the invention may also not contain any additional containing daily units and a given number of hormone-free folic acid, hoWever. daily units for uninterrupted daily oral administration to 20 To ensure that a Woman consumes the necessary amount of Women, characterized in that the hormone-containing daily folic acid or that her increased folic acid requirement at least units contain folic acid in a daily amount of at most 200 pg and at the beginning of pregnancy is met as quickly as possible if the hormone-free daily units in each case contain folic acid in she decides to try for a baby, so avoiding possible damage to a daily amount of >200 pg up to the maximum permissible the embryo due to a folic acid de?ciency, the hormone-free amount of folic acid for Women. 25 daily units of the folic acid dosage form according to the It is suspected that long-term taking of gestagen-based invention contain folic in an amount of more that 200 pg up to hormonal contraceptives may lead to a de?ciency of folic the maximum permissible daily amount of folic acid for acid. This de?ciency may lead to cardiovascular diseases, for Women, preferably up to 5 mg of folic acid per daily unit, example. particularly preferably of more than 200 pg to 5 mg folic acid, It is also knoWn that if pregnancy occurs a short time after 30 very particularly preferably up to the maximum permissible stopping taking such hormonal contraceptives, there is a risk daily amount of folic add for Women of reproductive age. that the de?ciency of folic acid may lead to neural tube By adding folic acid to the hormone-free daily units of the defects in the embryo. Since the neural tube develops in the dosage form according to the invention in amounts of up to ?rst Weeks of pregnancy, it is particularly advantageous to the maximum permissible amount, it is possible to increase ensure that folic acid is taken prior to conception. 35 the folic acid concentration in a Woman’s body While she is If, therefore, a Woman stops taking hormonal contracep taking the hormone-free daily units to the extent that the her tives because she Wants to have a child and she falls pregnant body’s increased folic acid requirement is met as quickly as in the ?rst cycle after stopping the hormonal contraceptives, it possible if she stops taking a hormone-containing contracep is particularly important to ensure an appropriately high level tive and then falls pregnant. of folic acid in the period directly after stopping taking the 40 The hormone-containing daily units of the dosage form “Pill”, as hormonal contraceptives are known. according to the invention preferably each contain the same There is therefore a need to add folic acid to hormonal amount of folic acid. This also applies to the hormone-free contraceptives in such a Way that the added folic acid is daily units, Which likeWise each contain the same amount of adapted to a Woman’s varying needs over the period during folic acid, this being greater than the amount contained in the and after a tablet-taking cycle. 45 hormone-containing daily units hoWever. 2. Brief Description of Related Developments The folic acid may also be present in the dosage form The combination of hormonal contraceptives and folic acid according to the invention as a pharrnaceutically safe salt, is already knoWn from W0 99/ 53910. The amount of folic preferably as sodium, potassium or salt, or as a acid per daily dose of merely matches the changes corresponding derivative. in a Woman’s folic acid requirements as she ages, and does not 50 Suitable derivatives of folic acid are mono- or diesters, take account of the changes in folic acid requirements over a Wherein the diesters may be differently or identically esteri contraceptive-taking cycle. ?ed. Suitable ester groups are preferably C l-C8 loW alkyl groups, such as methyl, ethyl, propyl or butyl, branched SUMMARY OF THE INVENTION Cl-C8 loW alkyl groups, such as isopropyl, isobutyl or sec. 55 butyl, cycloalkyl groups, such as cyclopentyl or cyclohexyl, It Was therefore the object of the present invention to pro aryl groups, such as phenyl or substituted phenyl With 1-2 vide a dosage form for hormonal contraception Which takes substituents, such as loW alkyl or haloalkoxyl groups, or account of the changes in folic acid requirements during a arylalkyl groups With Cl-C8 alkyl and aryl groups, such as hormone-taking cycle and subsequent hormone-free daily phenyl or substituted phenyl. units. 60 In addition, the hormone-free daily units and optionally the This object Was achieved by providing the dosage form hormone-containing daily units may contain further vitamins according to the invention for hormonal contraception con or minerals in addition to the folic acid. taining a given number of hormone-containing daily units and The number of daily units of a do sage form according to the a given number of hormone-free daily units for uninterrupted invention may correspond to a natural, monthly menstrual daily oral administration to Women, characterized in that the 65 cycle. In this case, the dosage form according to the invention hormone-containing daily units contain folic acid in a daily contains 21 to 25 hormone-containing daily units and 7 to 3 amount of at most 200 pg and the hormone-free daily units in hormone-free daily units. US 8,580,771 B2 3 4 However, it is also possible for the total number of hor The dosage forms according to the invention, especially the mone-containing daily units to correspond to more than a hormone-containing daily units, preferably comprise the fol Woman’s natural monthly cycle, such that a dosage form loWing hormone combinations: according to the invention may contain hormone-containing . 0.015 mg ethinyloestradiol+0.06 mg gestodene daily units to be taken Without interruption for up to 2 years, . 0.02 mg ethinyloestradiol+0.15 mg preferably up to 1 year, and 7 to 3 hormone-free daily units. . 0.02 mg ethinyloestradiol+0.5 mg HoWever, it is also possible for the dosage form according to . 0.02 mg ethinyloestradiol+1 mg chlormadinone acetate or the invention to comprise 42 to 52 or 77 to 193 hormone 2 mg or 3 mg chlormadinone acetate containing daily units alongside 7 to 3 hormone-free daily 5. 0.02 mg ethinyloestradiol+1 mg norethisterone units. 6. 0.03 mg ethinyloestradiol+1 mg norethisterone The hormone-containing daily units of the dosage form 7. 0.02 mg ethinyloestradiol+4 mg chlormadinone acetate 8. 0.02 mg ethinyloestradiol+5 mg chlormadinone acetate according to the invention may each contain at least one 9. 0.02 mg ethinyloestradiol+0.1 mg contraceptively acting hormone component, preferably a . 0.02 mg ethinyloestradiol+0.15 mg desogestrel combination of hormone components such as an oestrogen . 0.02 mg ethinyloestradiol+0.1 mg levonorgestrel and a gestagen. . 0.03 mg ethinyloestradiol+3 mg Oestrogens Which are suitable for the hormone-containing . 0.02 mg ethinyloestradiol+3 mg drospirenone daily units of the dosage form according to the invention are . 0.03 mg ethinyloestradiol+2 mg chlormadinone acetate preferably selected from the group comprising oestradiol, . 0.035 mg ethinyioestradiol+0.25 mg oestradiol valerate, ethinyloestradiol and . Ethiny 20 . 0.03 mg ethinyloestradiol+0.5 mg norethisterone ioestradiol is particularly preferred as the oestrogen for the . 0.03 mg ethinyioestradiol+0.15 mg desogestrel dosage form according to the invention. . 0.03 mg ethinyloestradiol+0.075 mg gestodene Gestagens Which are suitable for the hormone-containing . 0.03 mg ethinyioestradiol+0.15 mg levonorgestrel daily units of the dosage form according to the invention are . 0.03 mg ethinyloestradiol+0.15 mg desogestrel preferably selected from the group comprising norethister 25 . 0.03 mg ethinyloestradiol+0.15 mg levonorgestrel one, , norethisterone enantate, norges . 0.03 mg ethinyloestradiol+0.125 mg levonorgestrel timate, , levonorgestrel, gestodene, hydrox . 0.0375 mg ethinyloestradiol+0.75 mg lynestrenol yprogesterone caproate, acetate, . 0.03 mg ethinyloestradiol+1 mg norethisterone acetate, chlormadinone acetate, lynestrenol, . 0.03 mg ethinyloestradiol+0.5 mg norethisterone acetate, drospirenone, , desogestrel, 30 . 0.03 mg ethinyioestradiol+0.15 mg levonorgestrel progesterone, , , ethynodiol, . 0.04 mg ethlnyloestradiol+2 mg lynestrenol , acetate and . . 1st phase:7 days The hormones are preferably used in the amounts stated 0.050 mg desogestrel +0.035 ethinyloestradiol beloW. 2nd phase:7 days Oestrogens: 35 0.100 mg desogestrel +0.030 ethinyloestradiol 3rd phase:7 days 0.150 mg desogestrel +0.030 ethinyloestradiol 29. 1st phase:6 days Oestradiol, oestradiol valerate 0.5 to 4 mg Ethinyloestradiol 5 to 50 pg 0.03 mg EE +0.05 mg levonorgestrel Mestranol 8 to 70 pg 40 2nd phase:5 days 0.04 mg EE +0.075 mg levonorgestrel Gestagens: 3rd phase:10 days 0.03 mg EE +0.125 mg levonorgestrel 30. 1st phase:7 days 45 0.035 mg EE +0.180 mg norgestimate Norethisterone, norethisterone acetate 0.5 to 1.0 mg 2nd phase:7 days Norgestimate 0.1 to 0.25 mg 0.035 mg EE +0.215 mg norgestimate Norgestrel 0.3 to 1.0 mg Levonorgestrel 0.05 to 0.15 mg 3rd phase:7 days Gestodene 0.05 to 0.12 mg 0.035 mg EE +0.250 mg norgestimate Hydroxyprogesterone caproate 10 to 800 mg 50 31. 1st phase:6 days Medroxyprogesterone acetate 2.5 to 40 mg 0.03 mg EE +0.05 mg levonorgestrel 1.0 to 10 mg chlormadinone acetate 0.5 to 10 mg 2nd phase:5 days Lynestrenol 0.4 to 3 mg 0.04 mg EE +0.075 mg levonorgestrel 0.5 to 10 mg 3rd phase:10 days Drospirenone 1.0 to 10 mg 55 0.03 mg EE +0.125 mg levonorgestrel Dienogest 1.0 to 10 mg Desogestrel 0.06 to 0.30 mg 32. 1st phase:7 days Progesterone 100 to 1000 mg 0.035 mg EE +0.5 mg norethisterone Dydrogesterone 5 to 50 mg 2nd phase:9 days Medrogestone 2 to 30 mg 0.035 mg EE +1 mg norethisterone Ethynodiol, ethynodiol diacetate 0.4 to 3 mg 60 Promegestone 0.5 to 10 mg 3rd phase:5 days 0.5 to 10 mg 0.035 mg EE +0.5 mg norethisterone Trimegestone 1 to 10 mg 33. 1st phase:6 days 0.1 to 1 mg 0.03 mg EE +0.05 mg levonorgestrel 0.1 to 2 mg Norethynodrel 0.3 to 3 mg 2nd phase:5 days 1 to 10 mg 65 0.04 mg EE +0.075 mg levonorgestrel 3rd phase:10 days 0.03 mg EE +0.125 mg levonorgestrel US 8,580,771 B2 5 6 34 . 1st phase:7 days 55. 1st phase:6 days 0.035 mg EE+0.5 mg norethisterone 0.05 mg ethinyloestradiol+ 2nd phase:7 days 2nd phase:15 days 0.035 mg EE+0.75 mg norethisterone 0.05 mg ethinyloestradiol+1 mg norethisterone acetate 3rd phase:7 days m Where the dosage form according to the invention provides 0.035 mg EE+1 mg norethisterone a multiphasic hormone combination, it is recommended that 35 . 1st phase:6 days the hormone-containing daily units be taken Without inter 0.03 mg EE+0.05 mg levonorgestrel ruption only for a period of 21 to 25 days, followed by 7 to 3 2nd chase:5 days days of taking hormone-free daily units. 0.04 mg EE+0.075 mg levonorgestrel The dosage form according to the invention preferably 3rd phase:10 days comprises at least 21, preferably 21 to 25, hormone-contain 0.03 mg EE+0.125 mg levonorgestrel ing daily units Which preferably include 5 to 30 pg of ethiny 36 . 1st phase:6 days loestradiol and 0.5 to 5 mg of chlormadinone acetate, and 3 to 0.03 mg EE+0.05 mg levonorgestrel 7 hormone-free daily units. HoWever, the dosage form 2nd phase:6 days according to the invention may also comprise hormone-con 0.04 mg EE+0.075 mg levonorgestrel taining daily units for several years, preferably of 42 to 365 3rd phase:9 days units, Which contain the stated hormone combination in the 0.03 mg EE+0.125 mg levonorgestrel stated ranges, Wherein the corresponding uninterrupted tab 37 . 1st phase:6 days 20 let-taking periods are folloWed by 7 to 3 hormone-free daily 0.03 mg EE+0.05 mg levonorgestrel units With an elevated amount of folic acid stated according to 2nd phase:5 days the invention. 0.05 mg EE+0.05 mg levonorgestrel As already stated, the hormone-containing daily units of 3rd phase:10 days the dosage form according to the invention may take the form of a monophasic (one-phase) or multiphasic contraceptive. In 0.04 mg EE+0.125 mg levonorgestrel 25 the case of a multiphasic contraceptive, a tWo-phase or a 38 . 1st phase:6 days three-phase pill may be present, Which is not usually suitable, 0.03 mg EE+0.05 mg levonorgestrel hoWever, to be taken for a period longer than a Woman’s 2nd phase:5 days natural cycle. 0.04 mg EE+0.075 mg levonorgestrel 30 The dosage form according to the invention may also be a 3rd phase:10 days constituent of a kit, Wherein the kit according to the invention 0.03 mg EE+0.125 mg levonorgestrel may comprise a plurality of the dosage forms according to the 39 . 0.035 mg ethlnyloestradiol+2 mg cyproterone acetate invention, especially if one dosage form comprises only one 40 . 0.05 mg mestranol+2 mg chlorrnadinone acetate monthly cycle. The kit may optionally include a calendar or a 41 . 1st phase:11 days 35 diary. 0.05 mg ethinyloestradiol+1 mg chlorrnadinone acetate 2nd phase:1 1 days EXAMPLES 0.05 mg ethinyloestradiol+2 mg chlorrnadinone acetate 42. 0.08 mg mestranol+2 mg chlorrnadinone acetate Example 1 43. 0.03 mg ethlnyloestradiol+2 mg dienogest 40 44. 0.05 mg ethinyloestradiol+0.5 mg norgestrel a) Composition 45. 0.05 mg ethinyloestradiol+0.125 mg levonorgestrel 46. 0.05 mg ethinyloestradiol+0.25 mg levonorgestrel 47 . 0.05 mg ethinyloestradiol+0.125 mg levonorgestrel Per tablet 48. 0.05 mg ethinyloestradiol+1 mg norethisterone acetate 45 49 . 0.05 mg ethinyloestradiol+0.25 mg levonorgestrel Ethinyloestradiol 0.020 mg Chlormadinone acetate 2.000 mg 50. 1st phase:7 days Povidone K30 3.000 mg 0.04 mg ethinyloestradiol+0.025 mg desogestrel Lactose 31.980 mg 2nd phase:15 days Maize starch 12.000 mg 50 Magnesium stearate 0.500 mg 0.03 mg ethinyloestradiol+0.125 mg desogestrel Highly disperse silicon dioxide 0.500 mg 51 . 1 st phase:11 days 0.05 mg ethinyloestradiol+0.05 mg levonorgestrel 2nd phase:10 days Ethinyloestradiol (EE) and povidone K30 (polyvinylpyr rolidone) Were dissolved in 600 ml of ethanol. Chlormadi 0.05 mg ethinyloestradiol+0.125 mg levonorgestrel 55 none acetate (particle siZe 90% <50 um), lactose and maiZe 52 . 1st phase:11 days starch Were mixed in a mixer/pelletiser (Diosna P25) for 5 0.05 mg ethlnyloestradiol+0.05 mg levonorgestrel mins. and then moistened thoroughly and mixed With the 2nd phase:10 days ethanolic EE/PVP solution. The moist composition Was 0.05 mg ethinyloestradiol+0.125 mg levonorgestrel forced through a 3 mm screen and dried in a vacuum drying 53 . 1st phase:7 days 60 cabinet. The dried granular product Was disagglomerated 0.05 mg ethinyloestradiol+ through a 0.6 mm screen, mixed With magnesium stearate and 2nd phase:15 days highly disperse silicon dioxide and pressed on a tablet press 0.05 mg ethinyloestradiol+2.5 mg lynestrenol With 5 mm punches into tablets With a Weight of 50 mg. 54 . 1st phase:7 days b) As indicated under a), hormone-free, folic acid-contain 0.05 mg ethinyloestradiol+ 65 ing tablets With a Weight of 50 mg Were produced, Wherein the 2nd phase:15 days sodium salt of the folic acid Was dissolved in 600 ml of 0.05 mg ethlnyloestradiol+0.125 mg desogestrel aqueous ethanol. US 8,580,771 B2 7 8 4. A dosage form according to claim 1, wherein the dosage form comprises at least 21 hormone-containing daily units Per tablet and 7 to 3 hormone-free daily units. Sodium folate 3.000 mg 5. A dosage form according to claim 4, wherein the number Povidone K30 3.000 mg of hormone-containing daily units is suf?cient for adminis Lactose 31.000 mg tration for a maximum of 2 years, and the number of hor Maize starch 12.000 mg Magnesium stearate 0.500 mg mone-free daily units is suf?cient for administration for to 7 Highly disperse silicon dioxide 0.500 mg to 3 days. 6. A dosage form according to claim 4, comprising up to The tablets were coated with a methylhydroxypropylcel 730 hormone-containing daily units and 7 to 3 hormone-free lulose-based coating (e.g. Opadry YS-1-2184 made by Col daily units. orcon), coating composition 2 mg per tablet, and packaged 7. A dosage form according to claim 4, which comprises 21 into a dosage form comprising 120 hormone-containing daily to 25 hormone-containing daily units and 7 to 3 hormone-free units without folic acid and 7 hormone-free daily units with daily units. folic acid. 8. A dosage form according to claim 4, which comprises 42 What is claimed is: to 52 hormone-containing daily units and 7 to 3 hormone-free 1. A hormonal contraceptive do sage form for uninterrupted daily units. daily oral administration to women, said dosage form com 9. A dosage form according to claim 4, which comprises 77 prising hormone-containing daily units and hormone-free 20 to 193 hormone-containing daily units and 7 to 3 hormone daily units, wherein each of the hormone-containing daily free daily units. units comprises folic acid in a daily amount of from between 10. A dosage form according to claim 1, wherein the num about 5 to 200 ug and a combination of an oestrogen and a ber of hormone-containing daily units corresponds to a gestagen, and each of the hormone-free daily units comprises monophasic contraceptive. folic acid in a daily amount of greater than 200 ug up to the 25 11. A kit comprising at least one dosage form for hormonal maximum permissible amount of folic acid for women. contraception according to claim 1. 2. A dosage form according to claim 1, wherein the hor mone-free daily units each comprises more than 200 ug and 12. A kit according to claim 11, wherein the kit comprises up to 5 mg of folic acid. a plurality of dosage forms. 13. A dosage form according to claim 6, wherein the dos 3. A dosage form according to claim 1, wherein the hor 30 mone-containing daily units each comprises the same amount age form comprises up to 365 hormone-containing daily units of folic acid and the hormone-free daily units likewise each and 7 to 3 hormone-free daily units. comprises the same amount of folic acid. * * * * *